Efficacy of tivozanib treatment after sorafenib in patients with advanced renal cell carcinoma: crossover of a phase 3 study

Tivozanib is a selective inhibitor of vascular endothelial growth factor receptors 1, 2 and 3 tyrosine kinases. This open-label, crossover clinical study (AV-951-09-902) provided access to tivozanib for patients who progressed on sorafenib in TIVO-1, comparing tivozanib with sorafenib in patients with advanced renal cell carcinoma (RCC).

Patients enrolled in this single-arm, phase 2 crossover study were previously randomised to sorafenib on TIVO-1, progressed and then crossed over to tivozanib. Patients received tivozanib (1.5 mg/day orally; 3 weeks on/1 week off) within 4 weeks after their last sorafenib dose.

Crossover patients were exposed to tivozanib for a median of eight cycles. From the start of tivozanib treatment, median progression-free survival was 11.0 months (95% confidence interval [CI]: 7.3-12.7) and median overall survival was 21.6 months (95% CI: 17.0-27.6). Best overall response was partial response in 29 (18%) patients and stable disease in 83 (52%) patients, with a median duration of response of 15.2 and 12.7 months, respectively. About 77% of patients experienced adverse events, most frequently hypertension (26%), followed by diarrhoea (14%) and fatigue (13%); 53% of patients had treatment-related adverse events, including 24% grade ≥3. About 9% and 16% of patients had dose reductions and dose interruptions due to adverse events, respectively. A total of 30% of patients had serious adverse events, and 4% had treatment-related serious adverse events.

This crossover study of patients with advanced RCC demonstrated potent tivozanib anti-tumour activity. Safety and tolerability profiles were acceptable and consistent with the established adverse event profile of tivozanib.

European journal of cancer (Oxford, England : 1990). 2018 Mar 13 [Epub ahead of print]

Ana M Molina, Thomas E Hutson, Dmitry Nosov, Piotr Tomczak, Oleg Lipatov, Cora N Sternberg, Robert Motzer, Tim Eisen

Weill Cornell Medicine, New York, NY, USA. Electronic address: ., Texas Oncology-Baylor Charles A. Sammons Cancer Center, 3410 Worth Street, Suite 400, Dallas, TX, 75254, USA. Electronic address: ., N.N. Blokhin Cancer Research Center, Department of Clinical Pharmacology & Chemotherapy, 24 Kashirskoye Shosse, Moscow, 115478, Russia. Electronic address: ., Clinical Hospital Number 1 of Poznan University of Medical Sciences, Szamarzewskiego 82/84, 60-569, Poznan, Poland. Electronic address: ., Republican Clinical Oncology Dispensary, 73/1 Oktiabria Pr., Ufa, 450054, Russia. Electronic address: ., San Camillo-Forlanini Hospital, Department of Medical Oncology, Padiglione Flajani, 1st Floor, Circonvallazione Gianicolense 87, 00152, Rome, Italy. Electronic address: ., Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA. Electronic address: ., Cambridge University Health Partners, R4 Block, Box 193, Cambridge Biomedical Campus, Hills Road, Cambridge, England, CB2 0QQ, UK. Electronic address: .